Skip to main content
SpringerLink
Log in

Diabetes and Hypertension

  • Chapter
  • First Online:
Diabetes and Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Hypertension is a very common co-morbid condition in people with type 2 diabetes, particularly in the context of the metabolic syndrome that also includes dyslipidemia and visceral obesity leading to increased risk of cardiovascular disease (CVD) in this ever-growing diabetic populations in the USA and throughout the world. Hypertension in the diabetic populations has particular clinical characteristics, compared to hypertension in people without diabetes. These include as increased salt sensitivity, volume expansion, loss of nocturnal dipping of blood pressure and pulse, increased propensity to proteinuria, orthostatic hypotension, and isolated systolic hypertension. Most of these features are considered independent risk factors for CVD and are particularly important for designation of therapeutic strategies in this high-risk individuals. In this chapter, we provide an overview of the epidemiology, risk factors, and clinical characteristics of hypertension in people with diabetes. We also provide pathophysiologic insights in the mechanism of hypertension in this patient population paving the way to clear understanding to the rationale of the therapeutic strategies and the treatment guidelines that is largely based on evidence provided by randomized controlled trials. Students, residents, and busy practitioners will have a clear understanding of the major challenges in the management of hypertension in the diabetic population and strategies to mitigate the heightened CVD risk in these vulnerable populations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
eBook
USD 169.00
Price excludes VAT (USA)
Softcover Book
USD 159.99
Price excludes VAT (USA)
Hardcover Book
USD 219.99
Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. American Diabetes Association. Economic costs of diabetes in the U.S. in 2017. Diabetes Care. 2018;41(5):917–28.

    Article  PubMed Central  Google Scholar 

  2. Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clin Diabetes Endocrinol. 2017;3:1.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Geiss LS, Wang J, Cheng YJ, et al. Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980–2012. JAMA. 2014;312(12):1218–26.

    Article  CAS  PubMed  Google Scholar 

  4. CDC. National Diabetes Statistics Report 2020. Estimates of diabetes and its burden in the United States. 2020.

    Google Scholar 

  5. Zwald ML, Kit BK, Fakhouri THI, Hughes JP, Akinbami LJ. Prevalence and correlates of receiving medical advice to increase physical activity in U.S. adults: national health and nutrition examination survey 2013–2016. Am J Prev Med. 2019;56(6):834.

    Article  PubMed  PubMed Central  Google Scholar 

  6. McFarlane SI, Banerji M, Sowers J. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab. 2001;86:713–8.

    CAS  PubMed  Google Scholar 

  7. Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999;100:1134–46.

    Article  CAS  PubMed  Google Scholar 

  8. Blendea MC, McFarlane SI, Isenovic ER, Gick G, Sowers J. Heart disease in diabetic patients. Curr Diab Rep. 2003;3:223–9.

    Article  PubMed  Google Scholar 

  9. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.

    Article  CAS  PubMed  Google Scholar 

  10. Sowers JR, Epstein M, Frohlich E. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension. 2001;37:1053–9.

    Article  CAS  PubMed  Google Scholar 

  11. Gress TW, Nieto J, Shahar E, Wofford M, Brancati F. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med. 2000;342:905–12.

    Article�� CAS  PubMed  Google Scholar 

  12. Ford ES, Giles WH, Dietz W. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356–9.

    Article  PubMed  Google Scholar 

  13. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143–421. 3143–421.

    Google Scholar 

  14. Haffner S, Taegtmeyer H. Epidemic obesity and the metabolic syndrome. Circulation. 2003;108:1541–5.

    Article  PubMed  Google Scholar 

  15. Kereiakes DJ, Willerson J. Metabolic syndrome epidemic. Circulation. 2003;108:1552–3.

    Article  PubMed  Google Scholar 

  16. Moore JX, Chaudhary N, Akinyemiju T. Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Prev Chronic Dis. 2017;14:E24.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Alexander CM, Landsman PB, Teutsch SM, Haffner S. NCEP-defined metabolic syndrome diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes. 2003;52:1210–4.

    Article  CAS  PubMed  Google Scholar 

  18. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683–9.

    Article  CAS  PubMed  Google Scholar 

  19. Alberti KG, Zimmet PZ. Definition diagnosis and classification of diabetes mellitus and its complications. Part. 1998;15(7):539–53.

    CAS  Google Scholar 

  20. Groop L, Forsblom C, Lehtovirta M, et al. Metabolic consequences of a family history of NIDDM (the Botnia study): evidence for sex-specific parental effects. Diabetes. 1996;45:1585–93.

    Article  CAS  PubMed  Google Scholar 

  21. Meador M, Lewis J, Bay R, Wall H, Jackson C. Who are the undiagnosed? Disparities in hypertension diagnoses in vulnerable populations. Fam Community Health. 2020;43(1):35–45.

    Article  PubMed  Google Scholar 

  22. Verdecchia P, Porcellati C, Schillaci G, et al. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension. Hypertension. 1994;24:793–801.

    Article  CAS  PubMed  Google Scholar 

  23. Nakano S, Kitazawa M, Tsuda S, et al. INS resistance is associated with reduced nocturnal falls of blood pressure in normotensive, nonobese type 2 diabetic subjects. Clin Exp Hypertens. 2002;24:65–73.

    Article  PubMed  Google Scholar 

  24. Nielsen FS, Hansen HP, Jacobsen P, et al. Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy. Diabet Med. 1999;16:555–62.

    Article  CAS  PubMed  Google Scholar 

  25. Ohkubo T, Hozawa A, Yamaguchi J, et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens. 2002;20(11):2183–9.

    Article  CAS  PubMed  Google Scholar 

  26. White W. A chronotherapeutic approach to the management of hypertension. Am J Hypertens. 1996;9:29S–33S.

    CAS  PubMed  Google Scholar 

  27. Kario K, Okada K, Kato M, et al. 24-hour blood pressure-lowering effect of an SGLT-2 inhibitor in patients with diabetes and uncontrolled nocturnal hypertension: results from the randomized, placebo-controlled SACRA study. Circulation. 2018;139(18):2089–97.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Semplicini A, Ceolotto G, Massimino M, et al. Interactions between INS and sodium homeostasis in essential hypertension. Am J Med Sci. 1994;307:S43–6.

    PubMed  Google Scholar 

  29. Weinberger M. Salt sensitive human hypertension. Endocr Res. 1991;17:43–51.

    Article  CAS  PubMed  Google Scholar 

  30. Luft F, Miller J, Grim C, et al. Salt sensitivity and resistance of blood pressure: age and race as factors in physiological responses. Hypertension. 1991;17:I102–8.

    Article  CAS  PubMed  Google Scholar 

  31. Arun CS, Stoddart J, Mackin P, MacLeod JM, New JP, Marshall S. Significance of microalbuminuria in long-duration type 1 diabetes. Diabetes Care. 2003;26:2144–9.

    Article  PubMed  Google Scholar 

  32. Mitchell TH, Nolan B, Henry M, Cronin C, Baker H, Greely G. Microalbuminuria in patients with non-INS dependent diabetes mellitus relates to nocturnal systolic blood pressure. Am J Med. 1997;102:531–5.

    Article  CAS  PubMed  Google Scholar 

  33. Mogensen CE. Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes. J Intern Med. 2003;254:45–66.

    Article  CAS  PubMed  Google Scholar 

  34. Tagle R, Acevedo M, Vidt DG. Microalbuminuria: is it a valid predictor of cardiovascular risk? Cleve Clin J Med. 2003;70:255–61.

    Article  PubMed  Google Scholar 

  35. McFarlane SI, Farag A, Sowers J. Calcium antagonists in patients with type 2 diabetes and hypertension. Cardiovasc Drug Rev. 2003;21:105–18.

    Article  CAS  PubMed  Google Scholar 

  36. Streeten D, Anderson G Jr. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Aut Res. 1998;8:119–24.

    Article  CAS  Google Scholar 

  37. Streeten D, Auchincloss JH, Anderson G, Richardson R, Thomas FD, Miller J. Orthostatic hypertension. Pathogenetic studies. Hypertension. 1985;7:196–203.

    Article  CAS  PubMed  Google Scholar 

  38. Jacob G, Costa F, Biaggioni I. Spectrum of autonomic cardiovascular neuropathy in diabetes. Diabetes Care. 2003;26:2174–80.

    Article  PubMed  Google Scholar 

  39. Streeten DH. Pathogenesis of hyperadrenergic orthostatic hypotension: evidence of disordered venous innervation exclusively in the lower limbs. J Clin Invest. 1990;86:1582–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sowers JR, Bakris G. Antihypertensive therapy and the risk of type 2 diabetes mellitus. N Engl J Med. 2000;342(13):969–70.

    Article  CAS  PubMed  Google Scholar 

  41. Hypertension in Diabetes Study (HDS): I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications. 1993;11(3):309–17.

    Google Scholar 

  42. Mattock MB, Morrish NJ, Viberti G, Keen H, Fitzgerald AP, Jackson G. Prospective study of microalbuminuria as predictor of mortality in NIDDM. Diabetes. 1992;41(6):736–41.

    Article  CAS  PubMed  Google Scholar 

  43. Feldt-Rasmussen B, Mathiesen ER, Deckert T, et al. Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (INS-dependent) diabetes mellitus. Diabetologia. 1987;30(8):610–7.

    Article  CAS  PubMed  Google Scholar 

  44. Sowers J, Sowers P, Peuler J. Role of INS resistance and hyperINSemia in development of hypertension and atherosclerosis. J Lab Clin Med. 1994;123(5):647–52.

    CAS  PubMed  Google Scholar 

  45. Sowers JR. Effects of INS and IGF-1 on vascular smooth muscle glucose and cation metabolism. Diabetes. 1996;45:S47–51.

    Article  CAS  PubMed  Google Scholar 

  46. Sechi LA, Melis A, Tedde R. INS hypersecretion a distinctive feature between essential and secondary hypertension. Metabolism. 1992;41:1261–6.

    Article  CAS  PubMed  Google Scholar 

  47. Frohlich E. INS and INS resistance: impact on blood pressure and cardiovascular disease. Med Clin N Am. 2004;88:63–82.

    PubMed  Google Scholar 

  48. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron A. INS-mediated skeletal muscle vasodilation is nitric oxide dependent: a novel action of INS to increase nitric oxide release. J Clin Invest. 1994;94(3):1172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron A. Obesity/INS resistance is associated with endothelial dysfunction: implications for the syndrome of INS resistance. J Clin Invest. 1996;97(11):2601–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States 2000. Atlanta, GA: US Dept of Health and Human Services, Centers for Disease Control and Prevention; 2002.

    Google Scholar 

  51. Sowers JR. Obesity and cardiovascular disease. Clin Chem. 1998;44(Pt 2):1821–5.

    Article  CAS  PubMed  Google Scholar 

  52. Sowers J. Obesity as a cardiovascular risk factor. Am J Med. 2003;115(8A):375–415.

    Google Scholar 

  53. Sowers J. Diabetic nephropathy and concomitant hypertension: a review of recent ADA recommendations. Am J Clin Proc. 2002;3:27–33.

    Google Scholar 

  54. LeRoith D. INS-like growth factors. N Engl J Med. 1998;336:633–40.

    Article  Google Scholar 

  55. Sowers J. INS and INS-like growth factor in normal and pathological cardiovascular physiology. Hypertension. 1997;29:691–9.

    Article  CAS  PubMed  Google Scholar 

  56. Standley PR, Zhang F, Sowers J. IGF-1 regulation of Na+-K+-ATPase in rat arterial smooth muscle. Am J Phys. 1997;273:E113–21.

    CAS  Google Scholar 

  57. Hayashi K, Saga H, Chimori Y, Kimura K, Yamanaka Y, Sobue K. Differentiated phenotype of smooth muscle cells depends on signaling pathways through INS-like growth factor and phosphatidylinositol 3-kinase. J Biol Chem. 1998;273:28860–7.

    Article  CAS  PubMed  Google Scholar 

  58. Standley PR, Obards TJ, Martina C. Cyclic stretch regulates autocrine IGF-1 in vascular smooth muscle cells: implications in vascular hyperplasia. Am J Phys. 1999;276:E697–705.

    CAS  Google Scholar 

  59. El-Atat F, Aneja A, McFarlane S, Sowers J. Obesity and hypertension. Endocrinol Metab Clin N Amer. 2003;32:823–54.

    Article  CAS  Google Scholar 

  60. Jensen MD, Haymond MW, Rizza RA, Cryer PE, JM. M. Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest. 1989;83(4):1168–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma A. Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors. Diabetes. 2002;51(6):1699–707.

    Article  CAS  PubMed  Google Scholar 

  62. Hall JE, Hildebrandt DA, Kuo J. Obesity, hypertension: role of leptin and sympathetic nervous system. Am J Hypertens. 2001;14(6 pt 2):103S–15S.

    Article  CAS  PubMed  Google Scholar 

  63. Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with INS resistance and hyper INSemia. J Clin Endocrinol Metab. 2001;86(5):1930–5.

    Article  CAS  PubMed  Google Scholar 

  64. Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation. 2003;107(5):671–4.

    Article  CAS  PubMed  Google Scholar 

  65. Shuldiner AR, Yang R, Gong DW. Resistin obesity and INS resistance---the emerging role of the adipocyte as an endocrine organ. N Engl J Med. 2001;345(18):1345.

    Article  CAS  PubMed  Google Scholar 

  66. Sowers JR, Ferdinand KC, Bakris GL, Douglas J. Hypertension-related disease in African Americans: factors underlying disparities in illness and its outcome. Postgr Med. 2002;112(4):24–6.

    Article  Google Scholar 

  67. Li D, Sweeney G, Wang Q, Klip A. Participation of PI3K and atypical PKC in Na+,K+-pump stimulation by IGF-1 in VSMC. Am J Phys. 1999;276:H2109–16.

    CAS  Google Scholar 

  68. Sowers JR. Effects of INS and IGF-I on vascular smooth muscle glucose and cation metabolism. Diabetes. 1996;45(Suppl 3):S47–51.

    Article  CAS  PubMed  Google Scholar 

  69. Walsh MF, Barazi M, Sowers J. IGF-1 diminishes in vivo and in vitro vascular contractility: role of vascular nitric oxide. Endocrinology. 1996;137:1798–803.

    Article  CAS  PubMed  Google Scholar 

  70. Muniyappa R, Walsh MF, Sowers J. INS-like growth factor-1 increases vascular smooth muscle nitric oxide production. Life Sci. 1997;61:925–33.

    Article  CAS  PubMed  Google Scholar 

  71. Wu H, Jeng Y, Hsueh W. Endothelial-dependent vascular effects of INS and INS-like growth factor I in the perfused rat mesenteric artery and aortic ring. Diabetes. 1994;43:1027–32.

    Article  CAS  PubMed  Google Scholar 

  72. Zeng G, Nystrom FH, Quon MJ. Roles for INS receptor, PI3-kinase and Akt in INS-signaling pathways related to production of nitric oxide in human vascular endothelialc cells. Circulation. 2000;101:1539–45.

    Article  CAS  PubMed  Google Scholar 

  73. Sowers J. INS and INS-like growth factor-1 effects on CA2+ and nitric oxide in diabetes. In: Levin ER, Nadler JL, editors. Endocrinology of cardiovascular function. Boston, MA: Kluwer Academic Publishers; 1998. p. 139–58.

    Chapter  Google Scholar 

  74. Hasdai D, Rizza R, Holmes D, Richardson D, Cohen P, Lerman A. INS and INS-like growth factor-1 cause coronary vasorelaxation in vitro. Hypertension. 1998;32:228–34.

    Article  CAS  PubMed  Google Scholar 

  75. Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide in vascular endothelial cells. J Clin Invest. 1996;98(4):894–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Tirupattur P, Ram J, Standley P, Sowers J. Regulation of Na+,K(+)-ATPase gene expression by INS in vascular smooth muscle cells. Am J Hypertens. 1993;6:626–9.

    Article  CAS  PubMed  Google Scholar 

  77. Sowers JR, Draznin B. INS, cation metabolism and INS resistance. J Basic Clin Physiol Pharmacol. 1998;9:223–33.

    Article  CAS  PubMed  Google Scholar 

  78. Sowers J. Recommendations for special populations: diabetes mellitus and the metabolic syndrome. Am J Hypertens. 2003;16:41S–5S.

    Article  PubMed  Google Scholar 

  79. Zemel MB, Peuler JD, Sowers JR, Simpson L. Hypertension in insulin-resistant Zucker obese rats is independent of sympathetic neural support. Am J Phys. 1992;262(3 Pt 1):E368–71.

    CAS  Google Scholar 

  80. Henriksen EJ, Jacob S, Kinnick TR, Teachey MK, Krekler M. Selective angiotensin II receptor antagonism reduces insulin resistance in obese zucker rats. Hypertension. 2001;38(4):884–90.

    Article  CAS  PubMed  Google Scholar 

  81. Inishi Y, Katoh T, Okada T. Modulation of renal hemodynamics by IGF-1 is absent in spontaneously hypertensive rats. Kidney Int. 1997;52:165–70.

    Article  CAS  PubMed  Google Scholar 

  82. Isenovic ER, Muniyappa R, Sowers J. Role of PI3-kinase in isoproterenol and IGF-1 induced ecNOS activity. BBRC. 2001;285:954–8.

    CAS  PubMed  Google Scholar 

  83. Walsh MF, Sowers A. Vascular INS/INS-like growth factor-1 resistance in female obese Zucker rats. Metabolism. 2001;50:607–12.

    Article  CAS  PubMed  Google Scholar 

  84. Vecchione C, Colella S, Fratta L, et al. Impaired INS-like growth factor-1 vasorelaxant effects in hypertension. Hypertension. 2001;37:1480–5.

    Article  CAS  PubMed  Google Scholar 

  85. Isenovic ER, Jacobs DB, Kedees MH, et al. Angiotensin II regulation of the Na+ pump involves the phosphatidylinositol-3 kinase and p42/44 mitogen-activated protein kinase signaling pathways in vascular smooth muscle cells. Endocrinology. 2004;145(3):1151–60.

    Article  CAS  PubMed  Google Scholar 

  86. Sowers JR. Insulin resistance and hypertension. Am J Physiol Heart Circ Physiol. 2004;286:H1597–602.

    Article  CAS  PubMed  Google Scholar 

  87. Ouchi Y, Han S, Kim S, et al. Augmented contractile function and abnormal Ca2+ handling in the aorta of Zucker obese rats with INS resistance. Diabetes. 1996;45:S55–8.

    Article  CAS  PubMed  Google Scholar 

  88. Kolter T, Uphues I, Eckel J. Molecular analysis of INS-resistance in isolated ventricular cardiomyocytes of obese Zucker rats. Am J Phys. 1997;36:E59–67.

    Google Scholar 

  89. Ren J, Walsh MF, Sowers J. Altered inotrophic response to IGF-1 in diabetic rat heart: influence of intracellular Ca2+ and NO. Am J Phys. 1998;275:H823–30.

    CAS  Google Scholar 

  90. Dinmeter S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher A. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399:601–5.

    Article  Google Scholar 

  91. Leri A, Liu Y, Wang X, et al. Overexpression of INS-like growth factor-1 attenuates the myocyte renin-angiotensin system in transgenic mice. Circ Res. 1999;84:752–62.

    Article  CAS  PubMed  Google Scholar 

  92. Ren J, Jefferson L, Sowers J. Influence of age on contractile response to INS-like growth factor 1 in ventricular myocytes from spontaneously hypertensive rats. Hypertension. 1999;34:1215–22.

    Article  CAS  PubMed  Google Scholar 

  93. Ren J, Samson WK, Sowers JR. INS-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease. J Mol Cell Cardiol. 1999;31:2049–61.

    Article  CAS  PubMed  Google Scholar 

  94. Ren J, Sowers JR, Walsh MF, Brown RA. Reduced contractile response to INS and IGF-I in ventricular myocytes from genetically obese Zucker rats. Am J Phys. 2000;279:H1708–14.

    CAS  Google Scholar 

  95. Hemmings B. Akt signaling: linking membrane events to life and death decisions. Science (80-). 1997;275:628–30.

    Article  CAS  Google Scholar 

  96. Somwar R, Srimitani S, Klip A. Temporal activation of p70 S6 kinase and Akt1 by INS: PI3-kinasedependent and --independent mechanisms. Am J Phys. 1998;38:E618–25.

    Google Scholar 

  97. Begum N, Ragolia L, Rienzie J, McCarthy M, Duddy N. Regulation of mitogen-activated protein kinase phosphatase-1 induction by INS in vascular smooth muscle cells. J Biol Chem. 1998;273:25164–70.

    Article  CAS  PubMed  Google Scholar 

  98. Kaliman P, Canicio J, Begum N, Palacín M, Zorzano A. INS-like growth factor II, phosphatidylinositol 3-kinase, nuclear factor-KB and inducible nitric oxide synthase define a common myogenic signaling pathway. J Biol Chem. 1999;274(17):444.

    Google Scholar 

  99. Luo Z, Fujio Y, Kureishi Y, et al. Acute modulation of endothelial Akt/PKB activity alters nitric oxidedependent vasomotor activity in vivo. J Clin Invest. 2000;106:493–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Hermann C, Assmus B, Urbich C, Zeiher A, Dimmeler S. INS-mediated stimulation of protein kinase Akt: a potent survival signaling cascade for endothelial cells. Arter Thromb Vasc Biol. 2000;20:402–9.

    Article  CAS  Google Scholar 

  101. Begum N, Song Y, Rienzie J, ragolia L. Vascular smooth muscle cell growth and INS regulation of mitogenactivated protein kinase in hypertension. Am J Phys. 1998;275:C42–9.

    Article  CAS  Google Scholar 

  102. Villoso LA, Folli F, Sun XJ, White MF, Saad MJ, Kahn CR. Cross-talk between the INS and angiotensin signaling systems. Proc Natl Acad Sci U S A. 1996;93(12):495.

    Google Scholar 

  103. Isenovic E, Walsh MF, Muniyappa R, Bard M, Diglio CA, Sowers J. Phosphatidylinositol 3-kinase may mediate isoproterenol-induced vascular relaxation in part through nitric oxide production. Metabolism. 2002;51:380–6.

    Article  CAS  PubMed  Google Scholar 

  104. Lee MR, Li L, Kitazawa T. cGMP causes Ca2+ desensitization in vascular smooth muscle cells by activating the myosin light chain phosphatase. J Biol Chem. 1997;272:5063–8.

    Article  CAS  PubMed  Google Scholar 

  105. Begum N, Duddy N, Sandu OA, Reinzie J, Ragolia L. Regulation of myosin bound protein phosphatase by INS in vascular smooth muscle cells. Evaluation of the role of rho kinase and PI-kinase dependent signaling pathways. Mol Endocrinol. 2000;3:1365–76.

    Article  Google Scholar 

  106. Surks HK, Mochizuki N, Kasai Y, et al. Regulation of myosin phosphatase by a specific interaction with cGMP-dependent protein kinase 1alpha. Science (80-). 1999;286:1583–7.

    Article  CAS  Google Scholar 

  107. Sauzeau V, LeJeune H, Cario-Toumaniantz C, et al. Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem. 2000;275(21):729.

    Google Scholar 

  108. Kimura K, Ito M, Amano M, et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science (80-). 1996;273:245–8.

    Article  CAS  Google Scholar 

  109. Uehata M, Ishizaki T, Satoh H, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389(6654):990–4.

    Article  CAS  PubMed  Google Scholar 

  110. Yamakawa T, Tanaka A, Inagami T. Involvement of Rho-kinase in angiotensin II-induced hypertrophy of vascular smooth muscle cells. Hypertension. 2000;35:313–8.

    Article  CAS  PubMed  Google Scholar 

  111. Kitazawa T, Eto M, Woodsome TP, Brautigan D. Agonists trigger G protein-mediated activation of the CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility. J Biol Chem. 2000;275:9897–900.

    Article  CAS  PubMed  Google Scholar 

  112. Kawano Y, Fukata Y, Oshiro N, et al. Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-Kinase in vivo. J Cell Biol. 1999;147:1023–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Feng J, Ito M, Ichikawa K, et al. Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase*. J Biol Chem. 1999;274(52):37385–90.

    Article  CAS  PubMed  Google Scholar 

  114. Chibalin AV, Kovalenko MV, Ryder JW, Féraille E, Wallberg-Henriksson H, Zierath J. INS- and glucose-induced phosphorylation of the Na(+), K(+)-adenosine triphosphatase alpha-subunits in rat skeletal muscle. Endocrinology. 2001;42:3474–82.

    Article  Google Scholar 

  115. Sandu OA, Ito M, Begum N. Selected contribution: insulin utilizes NO/cGMP pathway to activate myosin phosphatase via Rho inhibition in vascular smooth muscle. J Appl Physiol. 2001;91:1475–82.

    Article  CAS  PubMed  Google Scholar 

  116. Berk B, Duff J, Marrero M. Angiotensin II signal transduction in vascular smooth muscle. In: Sowers JR, editor. Endocrinology of the vasculature. Totowa, NJ: Humana Press; 1996. p. 187–204.

    Chapter  Google Scholar 

  117. Dzau V. Tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis. Hypertension. 2001;37:1047–52.

    Article  CAS  PubMed  Google Scholar 

  118. Kureishi Y, Kobayashi S, Amano M, et al. Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation. J Biol Chem. 1997;272:1257–60.

    Article  Google Scholar 

  119. Folli F, Kahn R, Hansen H, Bouchie J, Feener E. Angiotensin II inhibits INS signaling in aortic smooth muscle cells at multiple levels. J Clin Invest. 1997;100:2158–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Clark E, King W, Brugge JS, Symons M, Hynes R. Integrin-mediated signals regulated by members of the rho family of GTPases. J Cell Biol. 1998;142:573–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sandu O, Ragolia L, Begum N. Diabetes in the Goto-Kakizaki rat is accompanied by impaired INS mediated myosin-bound phosphatase activation and vascular smooth muscle cell relaxation. Diabetes. 2000;49:2178–89.

    Article  CAS  PubMed  Google Scholar 

  122. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703–13.

    Google Scholar 

  123. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351(9118):1755–62.

    Article  CAS  PubMed  Google Scholar 

  124. Tuomilehto J, Rastenyte D, Birkenhager WH, et al. Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension: Systolic Hypertension in Europe Trial Investigators. N Engl J Med. 1999;340(9):677–84.

    Article  CAS  PubMed  Google Scholar 

  125. Curb JD, Pressel SL, Cutler JA, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension: Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA. 1996;276(23):1886–92.

    Article  CAS  PubMed  Google Scholar 

  126. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.

    Article  PubMed  Google Scholar 

  127. Arauz-Pacheco C, Parrott MA, Raskin P, American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003;26(Suppl 1):S80–2.

    PubMed  Google Scholar 

  128. Sowers JR, Haffner S. Treatment of cardiovascular and renal risk factors in the diabetic hypertensive. Hypertension. 2002;40:781–8.

    Article  CAS  PubMed  Google Scholar 

  129. Chobanian AV, Bakris GL, Black HR, National Heart, Lung, and Blood Institute, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, National High Blood Pressure Education Program Coordinating Committee. The seventh report of the joint national. JAMA. 2003;289(19):2560–72.

    Article  CAS  PubMed  Google Scholar 

  130. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA. 2014;311(5):507.

    Article  CAS  PubMed  Google Scholar 

  131. Rahman F, McEvoy JW, Ohkuma T, et al. Effects of blood pressure lowering on clinical outcomes according to baseline blood pressure and cardiovascular risk in patients with type 2 diabetes mellitus. Hypertension. 2019;73(6):1291–9.

    Article  CAS  PubMed  Google Scholar 

  132. Sacks FM, Svetkey LP, Vollmer WM, DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344(1):3–10.

    Article  CAS  PubMed  Google Scholar 

  133. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res. 1998;6(Suppl 2):51S–209S.

    Google Scholar 

  134. McFarlane SI, Shin JJ, Rundek T, Bigger J. Prevention of type 2 diabetes. Curr Diab Rep. 2003;3:235–41.

    Article  PubMed  Google Scholar 

  135. Eriksson KF, Lindgarde F. Prevention of type 2 (non-INS-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmo feasibility study. Diabetologia. 1991;34:891–8.

    Article  CAS  PubMed  Google Scholar 

  136. Helmrich SP, Ragland DR, Leung RW, Paffenbarger R Jr. Physical activity and reduced occurrence of non-INS-dependent diabetes mellitus. N Engl J Med. 1991;325:147–52.

    Article  CAS  PubMed  Google Scholar 

  137. Tuomilehto J, Lindstrom J, Eriksson JG, Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343–50.

    Article  CAS  PubMed  Google Scholar 

  138. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403.

    Article  CAS  PubMed  Google Scholar 

  139. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme in. JAMA. 2002;288(23):2981–97.

    Article  Google Scholar 

  140. Barzilay JI, Jones CL, Davis BR, et al. Baseline characteristics of the diabetic participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Diabetes Care. 2001;24:654–8.

    Article  CAS  PubMed  Google Scholar 

  141. McFarlane SI, Jacober SJ, Winer N, et al. Control of cardiovascular risk factors in patients with diabetes and hypertension at urban academic medical centers. Diabetes Care. 2002;25:718–23.

    Article  PubMed  Google Scholar 

  142. McFarlane SI, Kumar A, Sowers J. Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease. Am J Cardiol. 2003;91(12A):30H–7H.

    Article  CAS  PubMed  Google Scholar 

  143. Privratsky JR, Wold LE, Sowers JR, Quinn MT, Ren J. AT1 blockade prevents glucose-induced cardiac dysfunction in ventricular myocytes: role of the AT1 receptor and NADPH oxidase. Hypertension. 2003;42(2):206–12.

    Article  CAS  PubMed  Google Scholar 

  144. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE sub-study. Heart Outcomes Prevention Evaluation Study investigators. Lancet. 2000;355(9200):253–9.

    Google Scholar 

  145. Lindholm LH, Ibsen H, Dahlof B, LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):1004–10.

    Article  CAS  PubMed  Google Scholar 

  146. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363:2022–31.

    Article  CAS  PubMed  Google Scholar 

  147. Bakris GL, Weir M. Ace inhibitors and protection against kidney disease progression in patients with type 2 diabetes: what’s the evidence. J Clin Hypertens. 2002;4(6):420–3.

    Article  CAS  Google Scholar 

  148. Brenner BM, Cooper ME, de Zeeuw D, Investigators RENAAL Study. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.

    Article  CAS  PubMed  Google Scholar 

  149. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type. N Engl J Med. 2001;345(12):870–8.

    Article  CAS  PubMed  Google Scholar 

  150. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851–60.

    Article  CAS  PubMed  Google Scholar 

  151. Viberti G, Wheeldon NM, MicroAlbuminuria Reduction With VALsartan (MARVAL) Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation. 2002;106(6):672–8.

    Article  CAS  PubMed  Google Scholar 

  152. Mogensen CE, Neldam S, Tikkanen I, et al. Randomized controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321(7274):1440–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Palmer P. Renal dysfunction complicating the treatment of hypertension. N Engl J Med. 2002;347(16):1256–61.

    Article  PubMed  Google Scholar 

  154. Rake EC, Breeze E, Fletcher A. Quality of life and cough on antihypertensive treatment: a randomized trial of eprosartan, enalapril and placebo. J Hum Hypertens. 2001;15(12):863–7.

    Article  CAS  PubMed  Google Scholar 

  155. Gavras I, Gavras H. Are patients who develop angioedema with ACE inhibition at risk of the same problem with AT1 receptor blockers? Arch Intern Med. 2003;163(2):240–1.

    Article  PubMed  Google Scholar 

  156. Seferovic JP, Claggett B, Seidelmann SB, et al. Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial. Lancet Diabetes Endocrinol. 2017;5(5):333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001–7.

    Article  Google Scholar 

  158. Casiglia E, Tikhonoff V. Long-standing problem of β-blocker–elicited hypoglycemia in diabetes mellitus. Hypertension. 2017;70(1):42–3.

    Article  CAS  PubMed  Google Scholar 

  159. Dungan K, Merrill J, Long C, Binkley P. Effect of beta blocker use and type on hypoglycemia risk among hospitalized insulin requiring patients. Cardiovasc Diabetol. 2019;18(1):163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Kirpichnikov D, McFarlane SI, Sowers J. Heart failure in diabetic patients: utility of beta-blockade. J Card Fail. 2003;9(4):333–44.

    Article  CAS  PubMed  Google Scholar 

  161. Jacob S, Rett K, Wicklmayr M, Agrawal B, Augustin HJ, Dietze G. Differential effect of chronic treatment with two beta-blocking agents on INS sensitivity: the carvedilol-metoprolol study. J Hypertens. 1996;14(4):489–94.

    Article  CAS  PubMed  Google Scholar 

  162. Giugliano D, Acampora R, Marfella R, et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non-INS-dependent diabetes mellitus and hypertension: a randomized, controlled trial. Ann Intern Med. 1997;126(12):955–9.

    Article  CAS  PubMed  Google Scholar 

  163. Pasternak B, Svanström H, Hviid A. β-blockers in diabetic patients with heart failure—reply. JAMA Intern Med. 2015;175(4):657.

    Article  PubMed  Google Scholar 

  164. Intensive blood-glucose control with sulphonylureas or INS compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837–53.

    Google Scholar 

  165. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.

    Article  Google Scholar 

  166. Goldberg RB, Mellies MJ, Sacks FM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation. 1998;98(23):2513–9.

    Article  CAS  PubMed  Google Scholar 

  167. McFarlane SI, Muniyappa R, Francisco R, Sowers J. Clinical review 145: pleiotropic effects of statins: lipid reduction and beyond. J Clin Endocrinol Metab. 2002;87:1451–8.

    Article  CAS  PubMed  Google Scholar 

  168. Rolka DB, Fagot-Campagna A, Narayan KM. Aspirin use among adults with diabetes: estimates from the Third National Health and Nutrition Examination Survey. Diabetes Care. 2001;24(2):197–201.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Divisions of Endocrinology and Cardiovascular Medicine, SUNY-Downstate-Health Science University, Brooklyn, NY, USA

    Yuvraj Singh Chowdhury, Amirhossein Moaddab, Lina Soni & Samy I. McFarlane

  2. State University of New York, Downstate Medical Center, Brooklyn, NY, USA

    Samy I. McFarlane

Authors
  1. Yuvraj Singh Chowdhury
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amirhossein Moaddab
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lina Soni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Samy I. McFarlane
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samy I. McFarlane .

Editor information

Editors and Affiliations

  1. Steward St. Elizabeth’s Medical Center, Tufts University Medical School, Brighton, MA, USA

    Michael Johnstone

  2. Beth Israel Deaconess Medical Center / Harvard Medical School, Boston, MA, USA

    Aristidis Veves

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chowdhury, Y.S., Moaddab, A., Soni, L., McFarlane, S.I. (2023). Diabetes and Hypertension. In: Johnstone, M., Veves, A. (eds) Diabetes and Cardiovascular Disease. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-13177-6_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-13177-6_13

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-031-13176-9

  • Online ISBN: 978-3-031-13177-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation